Multimodal Treatments for Chronic Lower Back Pain

(BACPAC Trial)

Overseen By Sana Shaikh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Michigan

Must not be taking: High-dose opioids

Disqualifiers: Cancer, Pregnancy, Osteoporosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to identify the best treatments for individuals with chronic lower back pain lasting at least six months. Participants will initially engage with an online program called PainGuide before being assigned to one of four treatments: mindfulness-based stress reduction, physical therapy and exercise, self-administered acupressure, or the medication duloxetine (also known as Cymbalta, Yentreve, Drizalma Sprinkle, or Irenka). If the initial treatment proves ineffective, participants may try a second option. The trial aims to determine which treatments work best for different individuals based on their pain experiences. Participants should have back pain that disrupts daily life and must be open to trying any of the treatments offered. As a Phase 4 trial, the treatments are already FDA-approved and have proven effective, helping to understand how they benefit more patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must refrain from taking 'as needed' pain medications like NSAIDs, acetaminophen, and opioids for 8 hours before certain tests. It's best to discuss your specific medications with the study team.

What is the safety track record for these treatments?

Research has shown that duloxetine is generally safe for treating chronic low back pain, with many patients experiencing less pain and improved quality of life. Common side effects are usually mild and may include nausea or drowsiness.

Mindfulness-Based Stress Reduction (MBSR) offers another safe option. Research indicates it has no significant side effects and uses mindfulness meditation to help reduce pain.

Physical therapy and exercise provide safe ways to manage low back pain. These methods can lessen pain and improve movement with little risk.

Lastly, self-administered acupressure is safe and easy to perform at home. Studies have shown it has few to no side effects and can help reduce pain and fatigue.

Overall, these treatments are considered safe for most people with chronic low back pain. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these multimodal treatments for chronic lower back pain because they combine different therapies to provide a comprehensive approach. Unlike standard treatments like pain medications or physical therapy alone, these combinations include mindfulness-based stress reduction (MBSR), physical therapy (PT) and exercise, self-administered acupressure, and duloxetine in varied sequences. MBSR introduces a mental and emotional dimension by reducing stress, which can exacerbate pain. Acupressure, a self-help technique, empowers patients to manage their pain independently. By exploring these combinations, researchers hope to find synergies that offer better pain relief and improve quality of life more effectively than current options.

What evidence suggests that this trial's treatments could be effective for chronic lower back pain?

Research has shown that duloxetine, one of the treatments in this trial, can significantly reduce pain in individuals with long-term low back pain. It also improves quality of life and addresses mental health issues like depression. Mindfulness-based stress reduction (MBSR), another treatment option in this trial, has eased back pain and enhanced physical abilities over time. Physical therapy and exercise, also under study, effectively reduce pain and improve movement, with even better results when combined. Self-administered acupressure, another treatment under investigation, has demonstrated positive effects on pain and is easy to perform with minimal risk. Each of these treatments is being tested in this trial to manage chronic low back pain in various ways. ^{2 4 5 6 7}

Who Is on the Research Team?

Afton Hassett, PsyD

Principal Investigator

University of Michigan

Daniel Clauw, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for individuals with chronic lower back pain lasting at least six months, who are right-handed, can lie still for MRI scans, and don't have severe health issues like osteoporosis or uncontrolled addiction. Participants must not be pregnant, involved in other conflicting studies, expecting surgery within a year, or on high opioid doses.

Inclusion Criteria

I can avoid alcohol and nicotine on the day of my test.

You have had ongoing low back pain for at least six months, and it is present on more than half of those days.

I am open to being assigned any of the four treatment options.

Exclusion Criteria

I am not taking any medications that are excluded by the study.

You have a history that makes it unsafe for you to have an MRI scan.

You have had an allergic reaction to duloxetine in the past.

Timeline for a Trial Participant

Run-in

Participants complete a four-week run-in period using the PainGuide website

4 weeks

1 visit (in-person)

Treatment

Participants are randomized to one of four 8-week treatments: MBSR, PT and exercise, acupressure, or duloxetine

8 weeks

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

2 visits (in-person)

Additional Treatment

Participants with certain pain levels may be randomized to one of the three treatments not previously assigned

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Duloxetine
• MBSR
• PT and exercise
• Self-administered acupressure

Trial Overview The study tests four treatments: mindfulness-based stress reduction (MBSR), physical therapy with exercise, self-administered acupressure, and the medication duloxetine. After an initial assessment period using PainGuide and MRIs among others tools participants may receive two different treatments sequentially if they still have significant pain.

How Is the Trial Designed?

Group I: PainGuide Experimental Treatment 1 Intervention

Run-in treatment only with no additional treatments.

Group II: PT and exercise then MBSR Experimental Treatment 4 Interventions

Run-in treatment, then 8 weeks of PT and exercise, and then 8 weeks of MBSR.

Group III: PT and exercise then Duloxetine Experimental Treatment 4 Interventions

Run-in treatment, then 8 weeks of PT and exercise, and then approximately 8 weeks of Duloxetine

Group IV: PT and exercise then Acupressure Experimental Treatment 4 Interventions

Run-in treatment, then 8 weeks of PT and exercise, and then 8 weeks of Acupressure

Group V: PT and exercise Experimental Treatment 3 Interventions

Run-in treatment then PT and exercise

Group VI: MBSR then PT and exercise Experimental Treatment 4 Interventions

Run-in treatment then 8 weeks of MBSR, and then 8 weeks of PT and exercise.

Group VII: MBSR then Duloxetine Experimental Treatment 4 Interventions

Run-in treatment, then 8 weeks of MBSR, and then approximately 8 weeks of Duloxetine

Group VIII: MBSR then Acupressure Experimental Treatment 4 Interventions

Run-in treatment, then 8 weeks of MBSR, and then 8 weeks Acupressure.

Group IX: MBSR (mindfulness-based stress reduction) Experimental Treatment 3 Interventions

Run-in treatment then MBSR.

Group X: Duloxetine then PT and exercise Experimental Treatment 4 Interventions

Run-in treatment, then approximately 8 weeks of Duloxetine, and then 8 weeks of PT and exercise

Group XI: Duloxetine then MBSR Experimental Treatment 4 Interventions

Run-in treatment, then approximately 8 weeks of Duloxetine, and then 8 weeks of MBSR.

Group XII: Duloxetine then Acupressure Experimental Treatment 4 Interventions

Run-in treatment, then approximately 8 weeks of Duloxetine, and then 8 weeks Acupressure.

Group XIII: Duloxetine Experimental Treatment 3 Interventions

Run-in treatment then Duloxetine

Group XIV: Acupressure then PT and exercise Experimental Treatment 4 Interventions

Run-in treatment, then 8 weeks of Acupressure, and then 8 weeks of PT and exercise.

Group XV: Acupressure then MBSR Experimental Treatment 4 Interventions

Run-in treatment, then 8 weeks of Acupressure, and then 8 weeks of MBSR

Group XVI: Acupressure then Duloxetine Experimental Treatment 4 Interventions

Run-in treatment, then 8 weeks of Acupressure, and then approximately 8 weeks of Duloxetine

Group XVII: Acupressure Experimental Treatment 3 Interventions

Run-in treatment then Acupressure

Duloxetine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Approved in European Union as Cymbalta / Yentreve for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Diabetic Peripheral Neuropathic Pain
• Fibromyalgia
• Stress Urinary Incontinence

Approved in Canada as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8140818/

Duloxetine for the Treatment of Chronic Low Back Pain One study found no difference in back pain improvement with duloxetine 20 mg daily versus placebo (Table 3) [20]. Table 3. Efficacy outcomes.

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000206345

Efficacy and Safety of Duloxetine in Chronic Low Back Pain The total SF-36 score also showed a significant improvement in quality of life with duloxetine (MD: 3.63, 95% CI: [1.74 to 5.52], P= 0.0002).

3. bmcmusculoskeletdisord.biomedcentral.com bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-023-06488-6

Efficacy and safety of duloxetine in chronic musculoskeletal pain This meta-analysis improved that duloxetine can significantly reduce the pain level of patients, improve depressive symptoms and global impression,

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19469829/

A double-blind, randomized trial of duloxetine versus ... Duloxetine 60 mg was superior to placebo from weeks 3-11 in relieving pain, but not at weeks 12-13. Duloxetine 60 mg demonstrated significant improvement.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1526590010003871

Duloxetine Versus Placebo in Patients With Chronic Low ... Primary Efficacy Outcome. Compared with placebo treatment, duloxetine-treated patients showed a statistically significant (P ≤ .001) pain reduction, as measured ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3324928/

Efficacy and Safety of Duloxetine in Patients with Chronic ... This subgroup analysis assessed the efficacy of duloxetine in patients with chronic low back pain (CLBP) who did or did not use concomitant nonsteroidal ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/duloxetine-oral-route/description/drg-20067247

Duloxetine (oral route) - Side effects & dosage Duloxetine is used to treat depression and anxiety. It is also used for pain caused by nerve damage associated with diabetes (diabetic peripheral neuropathy).